Candidate T-Cell-Based Cancer Therapy Headed into Clinical Trials

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(ChemotherapyAdvisor) – A new T-cell-based drug overcomes immune tolerance to cancer and represents a new approach to tumor immunotherapy, according to researchers from Immunocore Ltd., Abingdon, Oxon, U.K. and the University of Pennsylvania, Philadelphia, PA. This conclusion is based on studies that culminated in the paper entitled “Monoclonal TCR-redirected Tumor Cell Killing,” which was published in Nature Medicine on May 6.

The study is based on two major lines of evidence, which were used to build the hypothesis. First, in patients diagnosed with cancer, eradication of malignant tumor cells and temporary clinical remission can occur as a result of the patient's T-cell-mediated cellular immune functions. However, T-cell-mediated anti-tumor functions only occur in a minority of patients, due to a failure of the specific T-cell receptor (TCR)–mediated immune recognition and activation process.

In this study, the investigators described the engineering and characterization of new anti-cancer reagents termed immune-mobilizing monoclonal TCRs against cancer (ImmTACs). Engineering led to the development of several ImmTACs, each designed by fusing a distinct tumor-associated epitope-specific monoclonal TCR to a humanized cluster of differentiation 3 (CD3)-specific single-chain antibody fragment (scFv).

Four of the ImmTACs tested “effectively redirected T-cells to kill cancer cells expressing extremely low surface epitope densities with picomolar affinity. Furthermore, these reagents potently suppressed tumor growth in vivo.”

The development of ImmTACs is based on 15 years of research to find a solution capable of detecting the low quantities of tumor-specific epitope on cancer cells. “ImmTACs overcome immune tolerance to cancer and represent a new approach to tumor immunotherapy,” the investigators concluded. Several ImmTac molecules will be in clinical trials in the United States and United Kingdom in late-2012.


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